This proposal describes a 5 year training program for the development of an academic career in Cardiovascular Disease. The principal investigator (PI) has completed structured fellowship training in Cardiology at the University of Pittsburgh and will expand upon his scientific skills through interdepartmental collaboration. This plan emphasizes training in cardiac physiology, pathology, endocrinology, and biochemistry at the gross and molecular levels through investigation of the importance of leptin signaling in the heart. Dr. Charles McTiernan is an Associate Professor in the Cardiovascular Institute (CVI) and a recognized leader in the field of heart failure (HF) and cytokine research. Dr. Christopher O'Donnell, Associate Professor in the Pulmonary Division, is an expert on the study of leptin and murine physiology in heart failure. Together, both Drs. McTiernan and O'Donnell have trained numerous students and fellows in the past and will mentor the Pi's scientific development. To enhance training and provide scientific and career advise, an interdepartmental advisory committee will be formed. Dr. Michael Mathier, Assistant Professor in the CVI, will provide training on the functional assessment of heart failure in mice. Dr. Robert O'Doherty, Assistant Professor in Biochemistry, will provide guidance in the areas of leptin physiology, signal transduction, and cre-lox technology. Dr. Jorge Sepulveda, Assistant Professor of Pathology, is an expert in the field of cardiac pathology and will provide training in techniques related to leptin histopathology. The research proposed is based on preliminary data that shows benefit to leptin on cardiac function and survival after myocardial infarction (Ml). Therefore, we hypothesize that leptin is protective after Ml. Specific aims designed to test this over-riding hypothesis and provide mechanistic understanding of leptin's benefit after Ml include using mice to: 1) Examine of the effect of leptin-deficiency and systemic leptin replacement on survival and the development of HF after Ml. 2) Compare systemic versus central effects of leptin administration in ob/ob mice on survival and the development of HF after Ml. 3) Examine the effect of cardiac specific deletion of the leptin receptor on survival and the development of HF after Ml. Overall, the CVI at UPMC provides an ideal environment for training physician scientists by encouraging inter-disciplinary collaboration and sharing of resources necessary for productive scientific discovery. (End of Abstract)